G-CSF/anti-G-CSF antibody complexes drive the potent recovery and expansion of CD11b+Gr-1+ myeloid cells without compromising CD8+ T cell immune responses

BACKGROUND: Administration of recombinant G-CSF following cytoreductive therapy enhances the recovery of myeloid cells, minimizing the risk of opportunistic infection. Free G-CSF, however, is expensive, exhibits a short half-life, and has poor biological activity in vivo. METHODS: We evaluated whether the biological activity of G-CSF could be improved by pre-association with anti-G-CSF mAb prior to injection into mice. RESULTS: We find that the efficacy of G-CSF therapy can be enhanced more than 100-fold by pre-association of G-CSF with an anti-G-CSF monoclonal antibody (mAb). Compared with G-CSF alone, administration of G-CSF/anti-G-CSF mAb complexes induced the potent expansion of CD11b(+)Gr-1(+) myeloid cells in mice with or without concomitant cytoreductive treatment including radiation or chemotherapy. Despite driving the dramatic expansion of myeloid cells, in vivo antigen-specific CD8(+) T cell immune responses were not compromised. Furthermore, injection of G-CSF/anti-G-CSF mAb complexes heightened protective immunity to bacterial infection. As a measure of clinical value, we also found that antibody complexes improved G-CSF biological activity much more significantly than pegylation. CONCLUSIONS: Our findings provide the first evidence that antibody cytokine complexes can effectively expand myeloid cells, and furthermore, that G-CSF/anti-G-CSF mAb complexes may provide an improved method for the administration of recombinant G-CSF

A Coordination Dynamics Approach to Test Multi-DOF Myoelectric Prostheses: Preliminary Results

<p>In this approach a reach-and-grasp task is studied from a coordination dynamics approach. We investigated whether differences between sound hand and prosthetic hand prehension are visible in coordination parameters of the shoulder and elbow joint. Preliminary data indeed showed that coordination patterns are more variable in the prosthetic hand condition. This finding could be used in future assessment of prosthetic technology.</p

Differences in Sound Hand and Prosthetic Prehension from a Coordination Dynamics Perspective

<p>Abstract Proceedings of Poster Presentation</p> <p>Proceedings of ISPO World Congress 2017 Cape Town, South Africa, p. 452, ISBN 978-87-93486-01-0</p

Pattern recognition myoelectric control: Evaluating EMG pattern separability

<p>Pattern recognition based myoelectric control for upper limb prostheses has gained increasing attention in the last years as it seems to offer more intuitive control than conventional, direct control. However, for such control to be feasible, the prosthesis user needs to have sufficient control of muscle contractions to create EMG patterns suitable for pattern classification. Few studies have investigated the relation between control ability and EMG pattern characteristics and an evaluation tool for quality of EMG patterns is still missing. We proposed such a tool and investigated whether scores from this tool were related to EMG pattern control ability.</p> <p>This poster was presented during the 2nd international symposium on innovations in amputations surgery and prosthetic technologies in Vienna, May 10-12, 2018.</p

Differences in Sound Hand and Prosthetic Prehension from a Coordination Dynamics Perspective

<p>More advanced prosthetic hands are entering the market, asking for new ways to gauge their performance. Natural and dexterous control are very important for patients and new control paradigms, such as pattern recognition, might facilitate this. Specifically naturalness of control and embodiment of the prosthesis are difficult to be directly and reliably measured, but studying joint angle coordination patterns might reveal those aspects.</p

UPPER LIMB MYOELECTRIC PROSTHESES: USER AND THERAPIST PERSPECTIVES ON QUANTIFYING BENEFITS OF PATTERN RECOGNITION CONTROL

<p>In this presentation results were shown of a qualitative study investigating user and therapist perceptions of state-of-the-art multi-function myoelectric upper limb prostheses and pattern recognition control.</p

The crux with reducing emissions in the long-term: The underestimated “now” versus the overestimated “then”

The focus of this perspective piece is on memory, persistence, and explainable outreach of forced systems, with greenhouse gas (GHG) emissions into the atmosphere serving as our case in point. In the light of the continued increase in emissions globally vis-à-vis the reductions required without further delay until 2050 and beyond, we conjecture that, being ignorant of memory and persistence, we may underestimate the “inertia” with which global GHG emissions will continue on their increasing path beyond today, thus, also leading to the amount of reduction that can be achieved in the future being overestimated. This issue is at the heart of mitigation and adaptation. For a practitioner, this translates to the problem of how persistently an emissions system behaves when subjected to a specified mitigation measure and which emissions level to adapt to for precautionary reasons in the presence of uncertainty. Memory allows us to reference how strongly the past can influence the “near-term future” of the system or (what we define as) its explainable outreach. We consider memory to be an intrinsic property of a system, retrospective in nature; and persistence to be a consequential (i.e., observable) feature of memory, prospective in nature and reflecting the tendency of a system to preserve a current state (including trend). Persistence depends on the system’s memory which, in turn, reflects how many historical states directly influence the current one. The nature of this influence can range from purely deterministic to purely stochastic. Different approaches exist to capture memory. We capture memory generically with the help of three characteristics: its temporal extent and both its weight and quality over time. The extent of memory quantifies how many historical data directly influence the current data point. The weight of memory describes the strength of this influence (fading of memory), while the quality of memory steers how well we know the latter (blurring of memory). Capturing fading and blurring of memory in combination is novel. In a numerical experiment with the focus on systemic insight, we cast a glance far ahead by illustrating one way to capture memory, and to understand how persistence plays out and how an explainable outreach of the system can be derived even under unfavorable conditions. We look into the following two questions: (1) Do we learn properly from the past? That is, do we have the right science in place to understand and treat memory appropriately? And (2) being aware that memory links a system’s past with its near-term future, do we quantify this outreach in a way that is useful for prognostic modelers and decision-makers? The latter question implies another question, namely, whether we can differentiate between and specify the various characteristics of memory (i.e., those mentioned above) by way of diagnostic data-processing alone? Or, in other words, how much system understanding do we need to have and to inject into the data-analysis process to enable such differentiation? Although the prime intention of our perspective piece is to study memory, persistence, and explainable outreach of forced systems and, thus, to expand on the usefulness of GHG emission inventories, our insights indicate the high chance of our conjecture proving true: being ignorant of memory and persistence, we underestimate, probably considerably, the “inertia” with which global GHG emissions will continue on their historical path beyond today and thus overestimate the amount of reductions that we might achieve in the future

Persistent anomalies of the extratropical Northern Hemisphere wintertime circulation as an initiator of El Niño/Southern Oscillation events

Climates across both hemispheres are strongly influenced by tropical Pacific variability associated with the El Niño/Southern Oscillation (ENSO). Conversely, extratropical variability also can affect the tropics. In particular, seasonal-mean alterations of near-surface winds associated with the North Pacific Oscillation (NPO) serve as a significant extratropical forcing agent of ENSO. However, it is still unclear what dynamical processes give rise to year-to-year shifts in these long-lived NPO anomalies. Here we show that intraseasonal variability in boreal winter pressure patterns over the Central North Pacific (CNP) imparts a significant signature upon the seasonal-mean circulations characteristic of the NPO. Further we show that the seasonal-mean signature results in part from year-to-year variations in persistent, quasi-stationary low-pressure intrusions into the subtropics of the CNP, accompanied by the establishment of persistent, quasi-stationary high-pressure anomalies over high latitudes of the CNP. Overall, we find that the frequency of these persistent extratropical anomalies (PEAs) during a given winter serves as a key modulator of intraseasonal variability in extratropical North Pacific circulations and, through their influence on the seasonal-mean circulations in and around the southern lobe of the NPO, the state of the equatorial Pacific 9–12 months later